Loss and Re-acquisition of Lytic Function by Cloned Cytotoxic T Lymphocytes: Role of Specific Antigen and Interleukin 2

We have previously reported the isolation of 2 human allospecific cytotoxic T-lymphocyte (CTL) elones that can undergo a reversible functional change from a highly lytic phase to a nonlytic quiescent phase and again to a lytic phase. The entire process was found to be regulated by recombinant interleukin 2 (rIL-2). We have now extended these studies in 3 ways. First, we show that specific alloantigens can also function as a signal to reactivate lytic function in the reverted CTL. However, in contrast to CTL reactivated with rIL-2, the antigen-reactivated CTL apparently fail to undergo subsequent cell division. Second, we have also found that this reversion phenomenon is not the same for all CTL tested, as 2 other CTL clones were found that did not revert to the non-lytie phase when cultured for up to 60 h in rIL-2-free medium. Third, the expression of Tac (IL-2 receptor) was also studied throughout the process of reversion and reactivation. rIL-2 added to the cell that had reverted to a non-lytic phase induced, an increase in the expression of Tac receptors during the reactivation phase, to levels greater than those expressed on cells continuously cultured in rIL-2-supplemented medium.